Lin Jason, Wu Shang-Chuen
Laboratory of Clinical Genomics, Chiba Cancer Center Research Institute, Chiba Cancer Center, Chiba 260-8717, Japan.
Division of Cell Therapy, Chiba Cancer Center Research Institute, Chiba Cancer Center, Chiba 260-8717, Japan.
Cancers (Basel). 2023 Feb 20;15(4):1332. doi: 10.3390/cancers15041332.
In the case of small-cell lung carcinoma, the highly metastatic nature of the disease and the propensity for several chromatin modifiers to harbor mutations suggest that epigenetic manipulation may also be a promising route for oncotherapy, but histone deacetylase inhibitors on their own do not appear to be particularly effective, suggesting that there may be other regulatory parameters that dictate the effectiveness of vorinostat's reversal of histone deacetylation. Recent discoveries that serotonylation of histone H3 alters the permissibility of gene expression have led to renewed attention to this rare modification, as facilitated by transglutaminase 2, and at the same time introduce new questions about whether this modification belongs to a part of the concerted cohort of regulator events for modulating the epigenetic landscape. This review explores the mechanistic details behind protein serotonylation and its possible connections to the epigenome via histone modifications and glycan interactions and attempts to elucidate the role of transglutaminase 2, such that optimizations to existing histone deacetylase inhibitor designs or combination therapies may be devised for lung and other types of cancer.
在小细胞肺癌的病例中，该疾病的高转移性以及几种染色质修饰因子易于发生突变的倾向表明，表观遗传调控或许也是肿瘤治疗的一条可行途径，但仅使用组蛋白去乙酰化酶抑制剂似乎效果并不显著，这表明可能存在其他调控参数决定着伏立诺他逆转组蛋白去乙酰化的有效性。近期的研究发现，组蛋白H3的5-羟色胺化会改变基因表达的可及性，这使得这种罕见的修饰再次受到关注，转谷氨酰胺酶2促进了这一过程，同时也引发了新的问题，即这种修饰是否属于调节表观遗传格局的协同调控事件群体的一部分。本综述探讨了蛋白质5-羟色胺化背后的机制细节，以及其通过组蛋白修饰和聚糖相互作用与表观基因组的可能联系，并试图阐明转谷氨酰胺酶2的作用，以便为肺癌和其他类型的癌症设计出对现有组蛋白去乙酰化酶抑制剂设计的优化方案或联合治疗方法。
